This proposal will study the neurohormonal regulation of thyrotropin secretion by the hypothalamus. This will be addressed by determining the pattern(s) of secretion of three putative thyrotropic neurohormones (thyrotropin-releasing hormone, somato-statin, and dopamine) under various physiologic conditions, and by elucidation of the sites of action of thyroid hormones within the hypothalamus. The newly developed technique of push/pull perfusion of the median eminence, serial blood sampling of unanesthetized rats, and thyroid receptor assay will be coordinated to develop an understanding of physiologic regulation of thyrotropin by the hypothalamus. Initial studies will be directed towards establishing the basal secretion of thyrotropin-releasing hormone (TRH), somatostatin (SS) and dopamine (DA) in the euthyroid rat, using the push/pull perfusion method. The physiologic importance of these hormones will be evaluated by observing changes in their secretion under conditions which alter thyrotropin release; rats will be exposed to cold (which causes release of TSH) and blood levels of thyroid hormones will be manipulated to determine the importance of particular neurohormones of each of these conditions. The regional distribution of hypothalamic sites responsive to feedback effects of thyroid will be evaluated by microinfusion of triiodothyronine into hypothalamic sites, and into the pituitary (as a control). Hypothalamic sites of thyroid action will also be determined by biochemical/anatomical methods; hypothalamic nuclei and the median eminence will be examined for their content of thyroid receptors in both nuclear and synaptsomal fractions, and for ability to intracellularly metabolize thyroxine to triiodothyronine. Later studies will evaluate site-specific influences on TRH, DA, and SS by feedback effects of triiodothyronine in specific hypothalamic loci; these studies will utilize the techniques of push/pull perfusion and microinfusion in unanesthetized rats. These studies will significantlyy enlarge our knowledge of hypothalamic participation in the neuroendocrine control of thyroid secretion.